tbuckley/cabot-search huggingface dataset:
pH-responsive hybrid platelet membrane-coated nanobomb with deep tumor penetration ability and enhanced cancer thermal/chemodynamic therapy
Authors: Huang Yang, Yuan Ding, Zongrui Tong, Xiaohui Qian, Hao Xu, Fenghao Lin, Guoping Sheng, Liangjie Hong, Weilin Wang, Zhengwei Mao
Journal: Theranostics (2022)

Background: Despite their outstanding properties in high surface-to-volume ratio and deep penetration, the application of ultrasmall nanoparticles for tumor theranostics remains limited because of their dissatisfied targeting performance and short blood circulation lifetime.Various synthetic materials with complex structures have been prepared as a multifunctional platform for loading ultrasmall nanoparticles.However, their use in nanomedicine is restricted because of unknown metabolic processes and potential physiological toxicity.Therefore, versatile and biocompatible nanoplatforms need to be designed through a simple yet effective method for realizing specific delivery and responsible release of ultrasmall nanoparticles.Methods: Iron-gallic acid coordination polymer nanodots (FeCNDs) exhibits outstanding photothermal ability and Fenton catalytic performance, which can be applied for tumor inhibition via hyperthermia and reactive oxygen species.A pH-responsive platelet-based hybrid membrane (pH-HCM) was prepared via co-extrusion and acted as a safe nanoplatform to load FeCNDs (pH-HCM@FeCNDs).Subsequently, their responsive performance and penetration ability were valued considering the multicellular sphere (MCS) model in an acidic or neutral environment.Thereafter, in vivo fluorescence image was performed to assess targeting capability of pH-HCM@FeCNDs.Finally, the corresponding antitumor and antimetastatic effects on orthotropic breast cancer were investigated.Results: In 4T1 MCS model, pH-HCM@FeCNDs group exhibited higher penetration efficiency (72.84%) than its non-responsive counterparts (17.77%) under an acidic environment.Moreover, the fluorescence intensity in pH-HCM@FeCNDs group was 3.18 times higher than that in group without targeting performance in the in vivo fluorescence image experiment.Finally, through in vivo experiments, pH-HCM@FeCNDs was confirmed to exhibit the best antitumor effect (90.33% tumor reduction) and antimetastatic effects (only 0.29% tumor coverage) on orthotropic breast cancer.Conclusions: Hybrid cell membrane was an ideal nanoplatform to deliver nanodots because of its good responsibility, satisfactory targeting ability, and excellent biocompatibility.Consequently, this study provides novel insights into the delivery and release of nanodots in a simple but effect method.
TRIB1 regulates tumor growth via controlling tumor-associated macrophage phenotypes and is associated with breast cancer survival and treatment response
Authors: Taewoo Kim, Jessica Johnston, Sonia Castillo-Lluva, Francisco J. Cimas, Stephen Hamby, Santiago Gonzalez-Moreno, Pedro Villarejo-Campos, Alison H Goodall, Guillermo Velasco, Alberto Ocana, Munitta Muthana, Endre Kiss-Toth
Journal: Theranostics (2022)

Molecular mechanisms that regulate tumor-associated macrophage (TAM) phenotype and function are incompletely understood.The pseudokinase TRIB1 has been reported as a regulator of macrophage phenotypes, both in mouse and human systems.Methods: Bioinformatic analysis was used to investigate the link between TRIB1 expression in breast cancer and therapeutic response to chemotherapy.In vivo models of breast cancer included immune-competent mice to characterize the consequences of altered (reduced or elevated) myeloid Trib1 expression on tumor growth and composition of stromal immune cell populations.Results: TRIB1 was highly expressed by TAMs in breast cancer and high TRIB1 expression correlated with response to chemotherapy and patient survival.Both overexpression and knockout of myeloid Trib1 promote mouse breast tumor growth, albeit through different molecular mechanisms.Myeloid Trib1 deficiency led to an early acceleration of tumor growth, paired with a selective reduction in perivascular macrophage numbers in vivo and enhanced oncogenic cytokine expression in vitro.In contrast, elevated levels of Trib1 in myeloid cells led to an increased late-stage mammary tumor volume, coupled with a reduction of NOS2 expressing macrophages and an overall reduction of macrophages in hypoxic tumor regions.In addition, we show that myeloid Trib1 is a previously unknown, negative regulator of the anti-tumor cytokine IL-15, and that increased myeloid Trib1 expression leads to reduced IL-15 levels in mammary tumors, with a consequent reduction in the number of T-cells that are key to anti-tumor immune responses.Conclusions: Together, these results define a key role for TRIB1 in chemotherapy responses for human breast cancer and provide a mechanistic understanding for the importance of the control of myeloid TRIB1 expression in the development of this disease.
Therapeutic angiogenesis-based strategy for peripheral artery disease
Authors: Jingxuan Han, Lailiu Luo, Olivia Marcelina, Vivi Kasim, Shourong Wu
Journal: Theranostics (2022)

Peripheral artery disease (PAD) poses a great challenge to society, with a growing prevalence in the upcoming years.Patients in the severe stages of PAD are prone to amputation and death, leading to poor quality of life and a great socioeconomic burden.Furthermore, PAD is one of the major complications of diabetic patients, who have higher risk to develop critical limb ischemia, the most severe manifestation of PAD, and thus have a poor prognosis.Hence, there is an urgent need to develop an effective therapeutic strategy to treat this disease.Therapeutic angiogenesis has raised concerns for more than two decades as a potential strategy for treating PAD, especially in patients without option for surgery-based therapies.Since the discovery of gene-based therapy for therapeutic angiogenesis, several approaches have been developed, including cell-, protein-, and small molecule drug-based therapeutic strategies, some of which have progressed into the clinical trial phase.Despite its promising potential, efforts are still needed to improve the efficacy of this strategy, reduce its cost, and promote its worldwide application.In this review, we highlight the current progress of therapeutic angiogenesis and the issues that need to be overcome prior to its clinical application.
PTRF/Cavin-1 enhances chemo-resistance and promotes temozolomide efflux through extracellular vesicles in glioblastoma
Authors: Eryan Yang, Lin Wang, Weili Jin, Xing Liu, Qixue Wang, Ye Wu, Yanli Tan, Yunfei Wang, Xiaoteng Cui, Jixing Zhao, Fei Tong, Biao Hong, Menglin Xiao, Xiaomin Liu, Chuan Fang, Chunsheng Kang
Journal: Theranostics (2022)

Background:The concentration and duration of intracellular drugs have always been the key factors for determining the efficacy of the treatment.Efflux of chemotherapeutic drugs or anticancer agents is a major reason for multidrug resistance generation in cancer cells.The high expression of polymerase I and transcript release factor (PTRF) is correlated with a worse prognosis in glioma patients.However, the importance of PTRF on temozolomide (TMZ) resistance in glioblastoma (GBM) is poorly understood.Methods: TCGA data analysis, CGGA data analysis, transmission electron microscopy (TEM), scanning electron microscopy (SEM), clone formation, cell counting kit-8 (cck-8), western blot (WB), immunofluorescence (IF), immunohistochemistry (IHC) and flow cytometry assays were performed to investigate the underlying mechanism and effect of PTRF on TMZ-resistance in a variety of GBM cell lines and GBM patient-derived xenograft (PDX) models.Clone formation, WB, IF, IHC and flow cytometry assays were performed to examine the efficacy of sequential therapy of TMZ followed by CQ in GBM cells and PDX models.Results: The prognosis of GBM patients treated with TMZ was negatively correlated with PTRF expression.Our results reveal that PTRF knockdown significantly decrease proliferation and increase apoptosis in GBM after TMZ treatment.Moreover, PTRF contribute to TMZ-resistance by increasing TMZ efflux through extracellular vesicles (EVs).Furthermore, our results demonstrate that sequential therapy of TMZ followed by CQ significantly promotes the TMZ efficacy against GBM by increasing intracellular TMZ concentration ([TMZ]i). Conclusion:This study highlights that PTRF can act as an independent biomarker to predict the prognosis of GBM patients after TMZ treatment and describes a new mechanism contributing to TMZ-resistance.In addition, this study may provide a novel idea for GBM therapy.
Annexin-A1 deficiency attenuates stress-induced tumor growth <i>via</i> fatty acid metabolism in mice: an Integrated multiple omics analysis on the stress- microbiome-metabolite-epigenetic-oncology (SMMEO) axis
Authors: Jianzhou Cui, Karishma Sachaphibulkij, Wen Shiun Teo, Hong Meng Lim, Li Zou, Choon Nam Ong, Rudi Alberts, Jinmiao Chen, Lina H. K. Lim
Journal: Theranostics (2022)

Background: High emotional or psychophysical stress levels have been correlated with an increased risk and progression of various diseases.How stress impacts the gut microbiota to influence metabolism and subsequent cancer progression is unclear.Methods: Feces and serum samples from BALB/c ANXA1 +/+ and ANXA1 -/-mice with or without chronic restraint stress were used for 16S rRNA gene sequencing and GC-MS metabolomics analysis to investigate the effect of stress on microbiome and metabolomics during stress and breast tumorigenesis.Breast tumors samples from stressed and non-stressed mice were used to perform Whole-Genome Bisulfite Sequencing (WGBS) and RNAseq analysis to construct the potential network from candidate hub genes.Finally, machine learning and integrated analysis were used to map the axis from chronic restraint stress to breast cancer development. Results:We report that chronic stress promotes breast tumor growth via a stress-microbiomemetabolite-epigenetic-oncology (SMMEO) axis.Chronic restraint stress in mice alters the microbiome composition and fatty acids metabolism and induces an epigenetic signature in tumors xenografted after stress.Subsequent machine learning and systemic modeling analyses identified a significant correlation among microbiome composition, metabolites, and differentially methylated regions in stressed tumors.Moreover, silencing Annexin-A1 inhibits the changes in the gut microbiome and fatty acid metabolism after stress as well as basal and stress-induced tumor growth.Conclusions: These data support a physiological axis linking the microbiome and metabolites to cancer epigenetics and inflammation.The identification of this axis could propel the next phase of experimental discovery in further understanding the underlying molecular mechanism of tumorigenesis caused by physiological stress.
TGFBI secreted by tumor-associated macrophages promotes glioblastoma stem cell-driven tumor growth via integrin αvβ5-Src-Stat3 signaling
Authors: Peng Peng, Hongtao Zhu, Dan Liu, Zirong Chen, Xiaolin Zhang, Zhongyin Guo, Minhai Dong, Lijun Wan, Po Zhang, Guohao Liu, Suojun Zhang, Fangyong Dong, Feng Hu, Fangling Cheng, Shijun Huang, Dongsheng Guo, Bin Zhang, Xingjiang Yu, Feng Wan
Journal: Theranostics (2022)

Rationale: In the glioblastoma (GBM) microenvironment, tumor-associated macrophages (TAMs) are prominent components and facilitate tumor growth. The exact molecular mechanisms underlying TAMs' function in promoting glioma stem cells (GSCs) maintenance and tumor growth remain largely unknown. We found a candidate molecule, transforming growth factor beta-induced (TGFBI), that was specifically expressed by TAMs and extremely low in GBM and GSC cells, and meanwhile closely related to glioma WHO grades and patient prognosis. The exact mechanism of TGFBI linking TAM functions to GSC-driven tumor growth was explored. Methods: Western blot, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IF), immunohistochemistry staining (IHC) and public datasets were used to evaluate TGFBI origin and level in GBM. The response of GSCs to recombinant human TGFBI was assessed in vitro and orthotopic xenografts were established to investigate the function and mechanism in vivo. Results: M2-like TAMs infiltration was elevated in high-grade gliomas. TGFBI was preferentially secreted by M2-like TAMs and associated with a poor prognosis for patients with GBM. TGFBI promoted the maintenance of GSCs and GBM malignant growth through integrin αvβ5-Src-Stat3 signaling in vitro and in vivo. Of clinical relevance, TGFBI was enriched in the serum and CSF of GBM patients and significantly decreased after tumor resection. Conclusion: TAM-derived TGFBI promotes GSC-driven tumor growth through integrin αvβ5-Src-Stat3 signaling. High serum or CSF TGFBI may serve as a potential diagnostic and prognostic bio-index for GBMs.
A general-purpose Nanohybrid fabricated by Polymeric Au(I)-peptide precursor to wake the function of Peptide Therapeutics: Erratum
Authors: Jin Yan, Fanpu Ji, Siqi Yan, Weiming You, Fang Ma, Fanni Li, Yinong Huang, Wenjia Liu, Wangxiao He
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.47243.].
Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging
Authors: Edoardo Lazzarini, Alessandra Maria Lodrini, Martina Arici, Sara Bolis, Sara Vagni, Stefano Panella, Azucena Rendon-Angel, Melissa Saibene, Alessia Metallo, Tiziano Torre, Giuseppe Vassalli, Pietro Ameri, Claudia Altomare, Marcella Rocchetti, Lucio Barile
Journal: Theranostics (2022)

Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence.These changes finally lead to adverse organ remodeling and resulting in heart failure.This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging.Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs.A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM.Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs.SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production.Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes.These effects were largely ascribable to augmented late sodium current (INaL) and reduced delayed rectifier potassium current (Ikr).Moreover sarcoplasmic reticulum (SR) Ca 2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca 2+ leak.Electrical and intracellular Ca 2+ alterations were mostly justified by increased CaMKII activity in SenCMs.Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones.Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca 2+ handling properties and metabolic features.Thus, Ivyspring
Essential role of IL-17 in acute exacerbation of pulmonary fibrosis induced by non-typeable <i>Haemophilus influenzae</i>
Authors: Shengsen Chen, Xinyun Zhang, Cheng Yang, Shi Wang, Hao Shen
Journal: Theranostics (2022)

Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) has a poor prognosis and lacks effective therapy.Animal models that mimic AE-IPF can greatly accelerate investigation of its pathogenesis and development of effective therapy.However, there are few reports of animal models of AE-IPF caused by bacteria.Thus, our study aimed to establish a mouse model of bacterium-induced AE-IPF and explore the potential pathogenic mechanism of AE-IPF.Methods: Mice were instilled intranasally with bleomycin (BLM) followed by non-typeable Haemophilus influenzae (NTHi) strain NT127.Murine survival, bacterial load, body weight and pulmonary histopathological changes were evaluated.We analyzed the T cell and inflammatory cell responses in the lungs.Results: Infection with 10 7 CFU NT127 triggered AE in mice with PF induced by 30 μg BLM.Compared with BLM-instilled mice, the BLM/NT127-treated mice showed more obvious airway inflammation, lower survival rate, higher inflammatory cell response, and increased proportions and numbers of IL-17 + CD4 + , IL-17 + γδ T, IL-22 + CD4 + and regulatory T (Treg) cells in lungs.γδ T cells were the predominant source of IL-17.IL-17 gene knockout mice with AE-IPF had quicker body weight recovery, milder pulmonary inflammation and fibrosis, stronger IL-22 + CD4 + T, TGF-β + γδ T and Treg cell responses, and weaker neutrophil and eosinophil responses than wild-type mice with AE-IPF.Conclusions: NTHi infection after BLM-induced IPF can cause AE-IPF in a murine model.This novel model can be used to investigate the pathogenesis of AE-IPF and develop new therapies for AE-IPF caused by bacteria.IL-17 is essential for the development of AE-IPF, and it may be a new therapeutic target for bacteria-induced AE-IPF.
DUSP2-mediated inhibition of tubular epithelial cell pyroptosis confers nephroprotection in acute kidney injury
Authors: Jiachuan Xiong, Li Ran, Yingguo Zhu, Yaqin Wang, Shaobo Wang, Yue Wang, Qigang Lan, Wenhao Han, Yong Liu, Yinghui Huang, Ting He, Yan Li, Li Liu, Jinghong Zhao, Ke Yang
Journal: Theranostics (2022)

Rationale: Acute kidney injury (AKI) is pathologically characterized by renal tubular epithelial cell (RTEC) death and interstitial inflammation, while their pathogenesis remains incompletely understood.Dual-specificity phosphatase 2 (DUSP2) recently emerges as a crucial regulator of cell death and inflammation in a wide range of diseases, but its roles in renal pathophysiology are largely unknown.Methods: The expression of DUSP2 in the kidney was characterized by histological analysis in renal tissues from patients and mice with AKI.The role and mechanism of DUSP2-mediated inhibition of tubular epithelial cell pyroptosis in AKI were evaluated both in vivo and in vitro, and confirmed in RTEC-specific deletion of DUSP2 mice.Results: Here, we show that DUSP2 is enriched in RTECs in the renal tissue of both human and mouse and mainly positions in the nucleus.Further, we reveal that loss-of-DUSP2 in RTECs not only is a common feature of human and murine AKI but also positively contributes to AKI pathogenesis.Especially, RTEC-specific deletion of DUSP2 sensitizes mice to AKI by promoting RTEC pyroptosis and the resultant interstitial inflammation.Mechanistic studies show that gasdermin D (GSDMD), which mediates RTEC pyroptosis, is identified as a transcriptional target of activated STAT1 during AKI, whereas DUSP2 as a nuclear phosphatase deactivates STAT1 to restrict GSDMD-mediated RTEC pyroptosis.Importantly, DUSP2 overexpression in RTECs via adeno-associated virus-mediated gene transfer significantly ameliorates AKI.Conclusion: Our findings demonstrate a hitherto unrecognized role of DUSP2-STAT1 axis in regulating RTEC pyroptosis in AKI, highlighting that DUSP2-STAT1 axis is an attractive therapeutic target for AKI.
Twist1 downregulation of PGC-1α decreases fatty acid oxidation in tubular epithelial cells, leading to kidney fibrosis
Authors: Limin Liu, Xiaoxuan Ning, Lei Wei, Ying Zhou, Lijuan Zhao, Feng Ma, Ming Bai, Xiaoxia Yang, Di Wang, Shiren Sun
Journal: Theranostics (2022)

Rationale: A deficiency of fatty acid oxidation (FAO) is the metabolic hallmark in proximal tubular cells (PTCs) in renal fibrosis owing to utilization of fatty acids by PTCs as the main energy source.Lipid accumulation may promote lipotoxicity-induced pathological injury in renal tissue.However, the molecular mechanism underlying lipotoxicity and renal tubulointerstitial fibrosis (TIF) remains unclear.Twist1 has been identified to play an essential role in fatty acid metabolism.We hypothesized that Twist1 may regulate FAO in PTCs and consequently facilitate lipotoxicity-induced TIF.Methods: We used hypoxia-induced Twist1 overexpression to incite defective mitochondrial FAO in PTCs, and used renal ischemia-reperfusion or unilateral ureteral obstruction to induce renal injury in mice.We used knockout cells, mice of Twist1, and Harmine to determine the role of Twist1 in FAO and TIF.Results: Overexpression of Twist1 downregulates the transcription of PGC-1α and further inhibits the expression of FAO-associated genes, such as PPARα, CPT1 and ACOX1.Consequently, reduced FAO and increased intracellular lipid droplet accumulation in a human PTC line (HK-2), leads to mitochondrial dysfunction, and production of increased profibrogenic factors.Twist1 knockout mice with renal injury had increased expression of PGC-1α, which restored FAO and obstructed progression of TIF.Strikingly, pharmacological inhibition of Twist1 by using Harmine reduced lipid accumulation and restored FAO in vitro and in vivo.Conclusion: Our findings suggest that Twist1-mediated inhibition of FAO in PTCs results in TIF and suggest that Twist1-targeted inhibition could provide a potential strategy for the treatment of renal fibrosis.
Phosphorus dendron nanomicelles as a platform for combination anti-inflammatory and antioxidative therapy of acute lung injury
Authors: Jin Li, Liang Chen, Changsheng Li, Yu Fan, Mengsi Zhan, Huxiao Sun, Serge Mignani, Jean-Pierre Majoral, Mingwu Shen, Xiangyang Shi
Journal: Theranostics (2022)

de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Pyroptosis in inflammatory diseases and cancer
Authors: Zhiping Rao, Yutong Zhu, Peng Yang, Zhuang Chen, Yuqiong Xia, Chaoqiang Qiao, Weijing Liu, Hongzhang Deng, Jianxiong Li, Pengbo Ning, Zhongliang Wang
Journal: Theranostics (2022)

Pyroptosis is a lytic and inflammatory type of programmed cell death that is usually triggered by inflammasomes and executed by gasdermin proteins. The main characteristics of pyroptosis are cell swelling, membrane perforation, and the release of cell contents. In normal physiology, pyroptosis plays a critical role in host defense against pathogen infection. However, excessive pyroptosis may cause immoderate and continuous inflammatory responses that involves in the occurrence of inflammatory diseases. Attractively, as immunogenic cell death, pyroptosis can serve as a new strategy for cancer elimination by inducing pyroptotic cell death and activating intensely antitumor immunity. To make good use of this double-edged sword, the molecular mechanisms, and therapeutic implications of pyroptosis in related diseases need to be fully elucidated. In this review, we first systematically summarize the signaling pathways of pyroptosis and then present the available evidences indicating the role of pyroptosis in inflammatory diseases and cancer. Based on this, we focus on the recent progress in strategies that inhibit pyroptosis for treatment of inflammatory diseases, and those that induce pyroptosis for cancer therapy. Overall, this should shed light on future directions and provide novel ideas for using pyroptosis as a powerful tool to fight inflammatory diseases and cancer.